Factors associated with improved survival in patients with wild-type transthyretin amyloid cardiomyopathy on tafamidis therapy
G Zemljic, S Frljak, T Bajec, P Girandon Susanj, N Zorz, A Cerar, R Okrajsek, G PoglajenAbstract
Introduction
Although tafamidis demonstrated clear clinical benefits in patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM), the patient- and disease-related factors associated with a favorable therapeutic response remain insufficiently characterized.
Purpose
To determine predictors of improved survival in tafamidis-treated wtATTR-CM patients.
Methods
We conducted a retrospective analysis of prospectively collected data from our institutional wtATTR-CM registry and included all consecutive patients with wtATTR-CM who initiated tafamidis therapy between April 1, 2021, and December 31, 2023. The primary endpoint was overall survival at 2 years. According to our institutional protocol, all patients with wtATTR-CM were followed in a dedicated outpatient clinic at 6-month intervals. At each follow-up visit, standardized clinical assessment, comprehensive biochemical testing, and electrocardiographic evaluation were systematically performed.
Results
Of 79 included patients, at 2 years 68 (86.1%) were alive (Group A), whereas 11 (13.9%) had died (Group B). There were no significant inter-group differences in age (76.4 ± 7.4 in Group A vs. 79.8 ± 4.2 years in Group B; P = 0.14), sex (male: 79% vs. 91%; P = 0.37), NYHA functional class (1.8 ± 0.3 vs. 2.0 ± 0.1; P = 0.07), or prevalence of permanent atrial fibrillation (46% vs. 64%; P = 0.27), arterial hypertension (68% vs. 64%; P = 0.80), and type 2 diabetes mellitus (15% vs. 18%; P = 0.77). Also, left ventricular end-diastolic volume (104 ± 31 mL vs. 105 ± 30 mL; P = 0.91) and left ventricular ejection fraction (56 ± 12% vs. 57 ± 16%; P = 0.86) did not differ between groups. However, patients in Group A exhibited significantly lower circulating NT-proBNP (2659 ± 2943 ng/L vs. 7027 ± 5289 ng/L; P = 0.0002), uric acid (375 ± 106 µmol/L vs. 495 ± 84 µmol/L; P = 0.0007) serum levels, and chitotriosidase (173 ± 185 nmol/L·h vs. 347 ± 183 nmol/L·h; P = 0.02) serum activity, together with higher estimated glomerular filtration rate (63.3 ± 15.0 mL/min/1.73m² vs. 51.6 ± 13.8 mL/min/1.73m²; P = 0.019), total protein (72.0 ± 4.7 g/L vs. 66.5 ± 6.4 g/L; P = 0.001), and albumin (45.1 ± 2.8 vs. 41.3 ± 3.3 g/L; P = 0.0001) serum levels. Echocardiographic evaluation further demonstrated a significantly lower left ventricular mass index (130 ± 29 g/m² vs. 163 ± 38 g/m²; P = 0.015) and lower E/e′ ratio (16.4 ± 6.4 vs. 22.7 ± 5.7; P = 0.02) in Group A compared to Group B.
Conclusion
In this real-world cohort of patients with wtATTR-CM, survival benefit at 2 years was primarily observed in individuals with less advanced disease at the time of tafamidis initiation. These findings suggest wtATTR-CM therapeutic interventions may be most effective when started early in the disease course and highlight the importance of timely disease detection and intervention in wtATTR-CM patients.